Mixed lymphocyte reaction blocking factors (MLR-Bf) as potential biomarker for indication and efficacy of paternal lymphocyte immunization in recurrent spontaneous abortion.

OBJECTIVES: The majority of cases of unexplained recurrent spontaneous abortion (RSA) remains unclear and is found to be associated with alloimmune antibodies termed as mixed lymphocyte reaction blocking factor (MLR-Bf). The decreased production of MLR-Bf may play major role in the immunologic failure of pregnancy and can lead to abortion. The present study was aimed at evaluating MLR-Bf as potential biomarker of indication and the efficacy of immunotherapy with paternal lymphocytes (LIT) in women with RSA. MATERIALS AND METHODS: A total of 97 women with history of unexplained RSA were recruited for this prospective study. These women showed negative for MLR-Bf and registered for lymphocyte immunotherapy with husband cells. Women with autoimmune pathology or anti-phospholipid syndrome were excluded. All individuals gave their consent to participate in the study. RESULTS: We have analyzed MLR proliferative response and MLR-Bf in nonpregnant women with history of RSA before and after LIT. Following LIT, the initially low MLR proliferative response was restored at 76.6 % of women, and MLR-Bf activity in blood serum could be detected in 74 % of women. The rate of successful pregnancy was shown to be significantly higher in women positive for MLR-Bf (50/72) as compared with the MLR-Bf negative women (7/25; χ (2) = 0.0003). CONCLUSION: The data obtained demonstrate that LIT with the paternal lymphocytes in MLR-Bf negative women is accompanied by increased proliferative cell response to the paternal alloantigens and by enhanced production of soluble suppressor activity factors (MLR-Bf) that is associated with improved pregnancy outcome in women with history of RSA.

[Natural killer cells lysing the blood B-lymphocytes of patients with chronic lympholeukemia]. / Estestvennye killernye kletki, liziruiushchie B-limfotsity krovi bol'nykh khronicheskim limfoleikozom.

The results of the study of natural cytotoxic activity of human peripheral blood lymphocytes are presented. Two types of natural killer cells isolated in discontinuous percoll density gradient have been shown to exist. Lymphocytes with low floating density lyse NK-sensitive target cells and leukemic B-lymphocytes, increase the lytic activity with respect to blasts of K-562 line under the effect of alpha-interferon. Lymphocytes isolated in percoll heavy fractions chiefly lyse leukemic B cells of patients by B-variant CLL and are not sensitive to the alpha-interferon effect.

[Antigen-specific immunotherapy as a component of combined therapy for malignant brain tumors]. / Antigenspetsificheskaia immunoterapiia v kompleksnom lechenii bol'nykh zlokachestvennymi opukholiami golovnogo mozga.

The purpose of the present research was to study immunity in the course of complex treatment for malignant gliomas of the brain and to evaluate extracorporeal antigen-specific immunotherapy (EASIT), a pilot procedure which was carried out according to an approved protocol. Initially, lowered HLA-DR+ monocyte count and in vitro inhibition of proliferative activity were reported in all patients. Inductive EASIT started in early postoperative period aborted immune disturbances caused by surgery. In 1998-2000, the procedure was performed in 33 patients with anaplastic astrocytoma (AA) (20) and glioblastoma (GB) (13). Mean dose of cell infusion was 2.43(0.18 x 109/patient and was well tolerated. There are 22 survivors and 9 patients died (GB--4 and AA--5; overall mortality--29%). Mean relapse-free survival was 14.2 mo (22); stable remission during 12-18 mo--37.5% (3/8)(GB) and 64% (9/14) (AA) Complete rehabilitation of immunity was generally reported 12 mo after the course of EASIT. Hence, complex treatment (surgery + EASIT) enhanced its efficacy in the management of brain tumors.

[Characteristics and immunologic changes in patients with malignant brain tumors]. / Kharakteristika i mekhanizmy immunnykh narushenii u bol'nykh so zlokachestvennymi opukholiami golovnogo mozga.

The investigation was concerned with assaying immunity and evaluating the role played by monocytes and tumor cells in the formation of T-cell dysfunction in malignant glioma (MG). The study group included 28 patients with anaplastic astrocytomas (n = 18) and glioblastomas (n = 10). MG patients showed significant changes in the numbers of CD16+ NK-cells and HLA-DR monocytes as well as lowered levels of HLA-DR expression on monocytes and proliferative response of T-lymphocytes as compared with both standard and alternative pathways of activation. Monocytes and macrophages suppressed T-cell activity due to production of prostaglandins E2 in such patients. Enhanced immunosuppression was also reported in 24-hour supernatants of tumor cells. Immune disorders were shown to involve apoptosis-independent mechanisms. Hence, despite the immune privilege of the brain, immunocompetent cells crossed blood-brain barrier and counteracted with tumor cells. As a consequence, monocyte function and cellular cooperation dropped while production of immunosuppressive factors rose, and T-cell dysfunction was brought about through apoptosis-independent mechanisms.

[Regulation of the natural killer activity of lymphocytes from healthy donors and patients with chronic lympholeukemia through the interaction of T- and non-T cells]. / Reguliatsiia natural'noi killernoi aktivnosti limfotsitov zdovorykh donorov i bol'nykh khronicheskim limfoleikozom putem vzaimodeistvii T- i ne-T-kletok.

The role of T- and B-cell cooperative interaction in the regulation of natural killer (NK) activity in human peripheral blood lymphocytes was studied. It has been shown that preincubation of normal donor mononuclear cells (MNC) for 48 h is followed by the loss of NK activity, while the incubation of the isolated T- and non-T-cell subsets does not lead to an analogous fall in the killer lymphocyte function. NK activity of MNC and isolated lymphocyte subsets in normal donors is shown to exceed that of CLL patients. The absence of preincubation effect on NK activity level of MNC, T- and non-T-cells in CLL patients has been also found. The findings obtained suggest that as a result of T- and B-cell interaction during preincubation differentiation of young T lymphocytes with NK cellular properties takes place. It is followed by the loss in NK activity. B-cell defect in CLL patients might cause the absence of preincubation effect on NK activity of T cells.

[Immunomodulating effect of locoregional cytokine therapy in patients with pulmonary tuberculosis]. / Immunokorrigiruiushchii éffekt lokoregional'noi tsitokinoterapii u bol'nykh tuberkulezom legkikh.

The immunomodulating effect of local and regional cytokine therapy was studied in patients with different forms of pulmonary tuberculosis. The signs of immunosuppression either preserve or progress with tuberculostatic chemotherapy (a control group). The inclusion of cytokine therapy into a treatment regimen for patients with pulmonary tuberculosis (an experimental group) assures complete correction of immune disorders in 30% of patients, as manifested by a significant increase in the absolute count of T lymphocytes, in the relative content of CD8 cells and monocytes with HLA-DR antigen expression. The most pronounced effect was achieved in patients with a fibrocavernous form of pulmonary tuberculosis. Immunological correction was accompanied by positive clinical and laboratory changes. Arrested intoxication, improved X-ray pattern of the lung, and ceased bacterial isolation were recorded in the patients. Positive clinical and immunological changes suggest that it is expedient to include local and regional cytokine therapy as part of treatment in patients with pulmonary tuberculosis.

[Specific features of immunity in patients with different forms of pulmonary tuberculosis]. / Osobennosti immuniteta u bol'nykh s razlichnymi formami tuberkuleza legkikh.

The cellular immunity was studied in 59 patients with pulmonary tuberculosis. The development of tuberculous infection was ascertained to be accompanied by decreases in the relative counts of CD9, CD8, and CD72 lymphocytes, as well as monocytes, expressing class II histocompatibility antigens (DR). The patients with tuberculosis were found to have suppressed proliferative T-cell activity and IL-2 production, moderately decreased IL-1 production and increased TNF alpha secretion.

[Involvement of nitric oxide in the development of tuberculin anergy in patients with pulmonary tuberculosis]. / Uchastie oksida azota v razvitii tuberkulinovoi anergii u bol'nykh tuberkulezom legkikh.

The production of nitric oxide (NO) and the magnitude of an antigen-specific proliferative response of the human lymphocytes stimulated by M. tuberculosis antigen [a purified protein derivative (PPD)] were investigated. PPD-reactive T lymphocytes were found in the peripheral blood of healthy donors. Normal values (mean values, the range of the minimum and maximum values) of PPD-induced proliferation and NO production were determined. Patients with pulmonary tuberculosis were found to have different levels of PPD-stimulated proliferation and NO production. The lymphocytes are shown to preserve their PPD reactivity in patients with normal NO production whereas the PPD-induced proliferative response was significantly decreased in those with high NO production. Patients with reduced tuberculin reactivities and high NO production were less responsive to treatment. The findings suggest that nitric oxide is involved in the development of tuberculin anergy with pulmonary tuberculosis.